The long history
of influenza does not indicate a close association between its epidemic
occurrences and major military undertakings. Because of the frequency
of both phenomena,
however, it is to be expected that they may at times coincide. The
appalling pandemic of 1918 in
the last months of the exhausting conflict of World War I, with massive
mobilization of armies
and upheaval of civilian populations, has irrevocably linked those two
catastrophes. It
demonstrated that virulent influenza may be more devastating of human
life than war itself.
Jordan2 has estimated that, in a few months, 20 million
people
perished; 548,000 in the United
States alone; the number attacked was 50 times as great. Among the
military personnel of the
United States there was "an estimated total of 24,853 deaths from
influenza as recorded, 469
from bronchitis, 10,341 from brochopneumonia, and 11,329 from lobar
pneumonia, a grand total
of 46,992. This is nearly as large a total as that of the battle
deaths, American Expeditionary
Forces--- 50,385." These deaths occurred among approximately
"797,993 cases of influenza,
272,735 of bronchitis, 37,334 of bronchopneumonia, and 51,115 of lobar
pneumonia, a total of
1,159,177 cases of respiratory diseases." 3
About 1 out of every 5 men contracted influenza in
the service.

Many students of
the disease have sought to explain the factors responsible for the
enormity of
that devastation. The clinical, pathologic, epidemiologic, and
bacteriologic data have been
voluminously recorded.4 It has in many quarters been
accepted as the
prototype of pandemic
influenza, an unwarrantable conclusion since this most exceptional
episode in the history of the
disease

1 The
author is greatly indebted to Col. John D. Morley, MC, USA (Ret.),
Resident Lecturer, Department of
Epidemiology, School of Public Health, University of Michigan, who gave
extensive assistance in reviewing
material and in the preparation of the graphs and tables dealing with
incidence.

cannot be considered typical. Among other criteria suggested as being
characteristic of
pandemic influenza in contrast to that of interpandemic years are (1) a
cycle of approximately 30
years; (2) the tendency for there to be three waves, the first a mild
widespread disease, the
second a severe autumnal epidemic with high fatality, the third of
lower incidence but high
fatality and less constant in occurrence; (3) a greater independence of
season; (4) greater and
more rapid dispersion; (5) a greater influence upon general mortality;
and (6) a different age
distribution so that the incidence in old people is less than that in
the younger, especially middle
age, groups. In many respects, these epidemiological generalizations
have few supporting data
other than those of 1918, and most of the other criteria appear to
measure severity of the disease.
Confronted with this vast occurrence and the lack of adequate
information as to the nature of the
causative agent, interpretations of the conditions responsible for the
1918 pandemic have
inevitably considered the dislocations and crowding of populations by
wartime conditions to be
essential elements in the development irrespective of the biologic
characteristics of the microbial
agent involved.

In the latter case,
the various bacterial pathogens of the respiratory tract were
extensively studied
and Hemophilus influenzae, while considered an important contributor to
severe disease, was not
believed to meet the requirements of the specific inciting agent of
the, epidemic. Realization of
the role of beta hemolytic streptococci and of staphylococci in severe
pulmonary disease. was
heightened. But beyond these was a progressive development of the idea
that a highly virulent
virus was involved, and a number of studies were made in efforts to
demonstrate its presence.
No conclusive or consistent results were obtained, even from the
intensive efforts of Rosenau
and others,5 to transmit
the disease to human volunteers. It is interesting and surprising that
apparently no material from patients was kept which could be subjected
to later study for virus.
Nevertheless, it seems probable that the autumnal epidemic of 1918 was
initiated by a virus of
high virulence in association with a high prevalence of potent
bacterial pathogens. It is unlikely
that this inciting agent was one with which the general population was
completely inexperienced
because all evidence emphasizes that the greatest proportion of the
population did not take sick,
indicating a resistance acquired earlier. Moreover, the fundamental
characteristics of the disease
clearly suggest that it was of similar behavior to influenza known
before and since that time. As
later data will make clear, the etiologic identity of the "waves"
cannot be unreservedly assumed.
Thomson and Thomson indicated that units affected in the spring
prevalence were relatively
resistant in the fall, although "seasoning" as such did not prevent
infection since veterans and
recruits were attacked in the autumn in organizations which had escaped
the spring experience.

The relative
helplessness with which prevention or treatment could be approached is
apparent.
Apart from the possible use of antipneumococcal serum in a limited
fashion for treatment of
specific cases, treatment was essentially palliative. A few studies
were concerned with the use
of convalescent serum. In the main, however, prompt bed rest, quiet,
and simplified diet were
relied upon. The handling of empyemas was revolutionized. In some
instances, an intelligent
effort was made to limit the opportunity for transmission of pathogens
by segregating, for
example, those with streptococcal infections from others. Along with
these went efforts to
prevent or reduce crowding by increasing space per man in barracks and
in transportation and by
avoiding congregations. The hygiene of housing and of person, together
with isolation and
quarantine, were the armamentarium of prevention.

Experience during
World War I

During the period of World War I and the pandemic of
influenza, one of the important agencies
utilized in the campaign against respiratory diseases was the Pneumonia
Board, appointed in
1918, at the request of The Surgeon General, by War Department
Special Order No. 118, 20
May 1918. Composed of civilian and military experts in the field of
respiratory and other
infectious diseases, this board rendered advisory services and
organized and directed
investigations at posts, camps, and hospitals. The Pneumonia Board was
a forerunner of the
Board for the Investigation and Control of Influenza and Other Epidemic
Diseases in the Army
which was established in 1941 through the initiative of the Preventive
Medicine Service, Office
of the Surgeon General.6 The latter
became known as the Army Epidemiological Board (p.94).

Influenza is not
especially a disease of wartime. However, conditions of mobilization,
mass
transportation, and crowding furnished a medium for the rapid spread
and accentuation in
severity of the disease. Because the microbial agents may be prevalent
on a post or may become
widely disseminated by transfer of personnel, influenza is a disease of
great hazard to military
effectiveness. Under these conditions, it appears that the military
forces may suffer
disproportionately iii comparison with civilian populations.

With this
perspective, the onset of another war inevitably recalled the specter
of 1918 and the
possibility that the development of similar or greater concentrations
of population would again
result in epidemiologic conditions which would heighten the severity of
influenza to a
catastrophic level. Influenza after 1918 had reverted to its normal
behavior of recurrent
epidemics at intervals of a few years, varying in distribution and
severity but commonly mild.
This increased the tendency to conclude that interpandemic influenza
was a different disease and
that influenza was in fact a clinical syndrome rather than a disease
entity.

6Bayne-Jones,
S.: Board for the Investigation and Control of Influenza and Other
Epidemic
Diseases in the Army. Army M. Bull. 64: 1-22, October
1942.

88

Experience
in 1919-39

Between 1919 and
1939, 12 epidemics of influenza were recorded 7 by the
United States Public
Health Service on the basis of excessive mortality accompanying sharp
epidemic waves of acute
respiratory disease. The most prominent were those of 1919-20, 1922-23,
1925-26, 1928-29,
1932-33, and 1936-37, but others such as 1935-36 were widespread. That
they were not
inconsiderable is indicated by the fact that the estimated excess
mortality from influenza and
pneumonia in the 1919-20 epidemic was 100,000 and, in 1928-29, 50,000.
Most of the
remainder exhibited sharp peaks but were less widely distributed. A
definite decline in
pneumonia mortality began about 1929 and continued except for a rise in
the epidemic period of
1935-37. Consequently, the scope of epidemics based upon excess
mortality is less clearly
demonstrated after 1930. A second interpretation for this alteration
could be offered; namely,
that the agent or agents of 1918 continued in prevalence through the
1928-29 epidemic and were
replaced by milder strains thereafter. Nevertheless, the 1937 period
had a sharp increase in
mortality.

The experience of
the Army during the interval between the two World Wars was not
significantly different from that of the civilian population, and the
mortality rates were extremely
low. The small strength, furthermore, would give little meaning to an
organizational rate except
as it reflected general experience. In the annual reports of The
Surgeon General, United States
Army, for 1929 and 1930, it was pointed out that since 1920 there had
been only the mild
epidemic of influenza in 1926 until 1928 when "there occurred a more
serious and generally
distributed epidemic * * *. A comparatively large percentage of
the strength of the Army was
affected * * *. "In December of 1928, a rate was reached of 523
per 1,000 white enlisted men in
the United States; in January 1929, the rate was 336. The annual
admission rates are less
informative, since they bisect the epidemic, but that of 81.7 per 1,000
for 1928 is the highest of
the decade 1920-29. The rates for pneumonia and common respiratory
disease during these
years were also among the highest for the decade. The death rate from
pneumonia and influenza
was, however, not proportionately elevated.

Special attention
is called to a year such as 1936 when, in certain regions among the
civilian
population, influenza reached the level of sharp epidemics during the
early months; then in
December the peak of the 1936-37 pandemic spread was rapidly
approached. The first was
influenza B, the second influenza A.8
The latter was worldwide and typically influenzal.
Moreover, it was

7
(1) Collins, S. D.:
Influenza-Pneumonia Mortality in a Group of About 95 Cities in the
United States, 1920-29.Pub.Health Rep. 45:361-406, 21 Feb. 1930. (2)
Collins, S. D., and Gover, M.: Influenza and Pneumonia Mortality
in a Group of About 95 Cities in the United States During Four Minor
Epidemics, 1930-35, With a Summary for
1920-35.Pub. Health Rep. 50:1.668-1689, 29 Nov. 1935. (3) Gover, M.:
Influenza and Pneumonia Mortality in a
Group of 90 Cities in the United States, August 1935-March 1943.
With a Summary for August 1920-March 1943. Pub. Health Rep.
58. 1033-1061, 9 July 1943. (4) Collins, S. D.: Age
and Sex Incidence of Influenza in the Epidemic of 1943-44, With
Comparative Data for Preceding Outbreaks.Pub. Health Rep. 59:
1483-1503, 17 Nov. 1944. (5) Collins, S. D.:
Influenza and Pneumonia Excess Mortality at Specific Ages in the
Epidemic 1943-44, With Comparative Data for
Preceding Epidemics. Pub. Health Rep. 60: 821-835, 20 July; 853-863, 27
July 1945.

identified etiologically in many
parts of the world. Among white enlisted men in the Army in the
United States, the admission rate for 1937 rose to 50.1 per 1,000
average strength, but seasonal
data are not available. There is evidence, nevertheless, that the
1936-37 epidemic was sharply
expressed in the Army, although no significant increase in mortality
occurred. In 1938-39, a mild
prevalence of a spotty nature was present (charts 12 and 13).

Influenza, then,
in the 20 years since 1919 had returned to its former status of
recurrent
epidemics at short intervals, often so mild as to be unnoticed but with
certain episodes of
pandemic distribution and of sufficient severity to cause considerable
alarm and disturbance in
the general population. That it was a disease of potential severity was
clearly apparent since even
the mild prevalences tended to cause a heightened mortality from
respiratory disease. The excess
mortality remained a valuable index of the spread and severity of
epidemics and even of their
recognition. Reports based upon clinical diagnosis were, as always,
unreliable since many
factors, including publicity or special instructions, had a large
influence in this respect. Army
data show this effect clearly, as will be illustrated later, in the
lack of reports of influenza from
some areas when an epidemic was known to be occurring, or high reports
of influenza in
prevalences of acute respiratory disease known not to be identifiable
as influenza. However, in
most instances, the character of the epidemic curve and the
distribution among troops of abrupt
rapid epidemics of nonbacterial acute respiratory disease readily
suggest its nature. The
occurrence of the disease and the factors which govern it remained
essentially unaffected at the
onset of World War II
.

The Army began its
expansion program in 1940, and the draft was adopted. The increase in
strength began slowly in June, then rapidly in October, November, and
December. This and the
industrial program brought together a large number of individuals from
diversified areas under
conditions furnishing ready opportunity for the rapid spread of
respiratory infections. However,
in general, the health of the Army and the United States during this
period was excellent.

Early in 1940, a
limited epidemic of mild influenza occurred, first in the Southeastern
States and
shortly afterward in New York. This was the out break from which
influenza virus, type B, was
first isolated.9 In the civilian
population, it was said to be limited to the eastern part of the
United States, but serologic data demonstrated it to be more widely
dispersed.10 The admission
rates for influenza in the Army show a moderate rise in the Third,
Fourth, and Fifth Corps Areas
during the months of January and February. In general, the United
States Army within the
continental limits had a low incidence of influenza for the first half
of the year as compared with
the previous

5-year average. The admission rate
for common respiratory diseases for the same period,
however, was in general higher than the 5-year average. Influenza B was
recognized in southern
England,11 and, in the summer of 1940, it
was prevalent in Cuba.12 The
recognition of this disease
and means for identification were extremely important for proper
understanding of the problem.

In June and July
1940, well-marked epidemics of influenza A occurred in Cuba and Puerto
Rico.
There was a sharp rise in the admission rate to 126.4 for influenza
among the Puerto Rican
troops in June followed by a moderate rise to 93.9 in July among the
continental troops stationed
on the island, but in August no cases were reported.

At this same time,
an epidemic of mild influenza was reported from Argentina.13
This outbreak
reached its peak in the Argentine Navy in the week ending 21 July 1940,
in the Army during the
following week, and in the civilian population in the week ending 4
August.

In August, the
admission rates for influenza showed a sudden rise in the Philippine
Islands. The
incidence during the month was twice as high among Filipino troops as
that reported for United
States troops stationed there. Unfortunately, the data for admissions
in the overseas departments
are not available for the remaining months of 1940 (September to
December).

During 1940 in
Australia, especially in military camps, extensive epidemics of
pharyngitis and
tracheitis occurred. Influenza was not isolated until September when
more typical cases
occurred in a military camp and in a small hospital outbreak.14

Influenza was
noted in Hawaii in the
middle of September 1940 and declared epidemic on 26
September. Reporting was then made mandatory until 31 December.
Approximately 16,500
cases were reported. The majority of these were from the island of
Oahu, including Honolulu. The epidemic peaked sharply during the middle
of October. Doolittle 15 stated the
impression
that the disease came from the West and suggested that it was
introduced by a Japanese training
ship from the Japanese Mandated Islands where an epidemic was
prevalent. The influenza
incidence among white enlisted troops stationed in Hawaii during 1940
was 65.3 per 1,000
average strength per year. The highest incidence for white enlisted
melt for the year was
reported in the United States (77.6) with Hawaii in second place.

In November 1940,
the admission rates for influenza in the Ninth Corps Area showed a
sharp
rise which reached its peak in the 4-week period of

December. During this same period,
the Fifth Corps Area had a very high incidence (1,444 per
1,000 per annum based on the 4-week period). The Eighth Corps Area also
recorded its highest
rates during December. The other six corps areas reached their highest
incidence during the 5-week period of January 1941. The First, Second,
and Sixth Corps Areas lead a relatively low
number of cases of diagnosed influenza (below 200 cases per 1,000 per
annum in the highest
period), although definite epidemic peaks were attained. The rate of
admissions in white enlisted
men in the United States was 77.6 for 1940, which was approximately
four times that for 1939,
20.3. Admissions for common respiratory disease in each corps area,
except the Fifth Corps
Area, showed a sharp rise coincident with the rise in influenza. The
incidence of these diseases
remained generally high until March in contrast with the much more
rapid subsidence of
influenza. The combined annual rate for common respiratory diseases and
influenza was nearly
1,200 for the entire Army in the United States for 1940-41 (chart 14).

A widespread
epidemic of influenza occurred in the civilian population at the same
time.16 The
notable feature of this outbreak was the rapidity of spread from the
Pacific Coast eastward
throughout the United States and Canada. The peak of incidence in the
Pacific Coast States was
reached in mid-December. The West South Central and Mountain States
reached their peak in
late December or the first week in January, the East South Central and
South Atlantic States the
second week in January, and the East North Central and Middle Atlantic
States during the third
week of January. However, the New England States reached their
peak during the second week
in January. The spread of the disease as shown in the Metropolitan Life
Insurance Company
survey 17 seemed to follow three main paths: (1) The
southernmost route
across the Southern
and Gulf States spread most rapidly and showed the most ordered
progress; (2) the path across
the middle of the country was not quite as rapid; (3) the northernmost
route showed the slowest
rate. The peak of the incidence in South Dakota was in early February
and in Iowa and
Wisconsin in mid-February. As the admission rates for the Army are
given for 4- or 5-week
periods, no such orderly progress of the disease was discernible.

Clinically the
disease was a mild acute febrile illness with abrupt onset associated
with mild
myalgia, some lassitude, but little prostration. Complications were
rare. Of 19,609 cases
occurring among Army personnel in the United States, 57 developed
pneumonia. Only 1 death
from influenza was reported in the Army for 1940 and only 3 deaths from
acute primary
pneumonia.

The excess
mortality recorded in the
civilian population was slight, but, according to the
recorded rates of the Army in the continental United States, this was
the highest epidemic of the
war period.

It was during this
explosive outbreak of influenza that the planning and guidance
exercised by
the reorganized Preventive Medicine Service, Office of the Surgeon
General, under the
immediate direction of Lt. Col. (later Brig. Gen.) James S. Simmons,
MC, resulted in the
development of a new and powerful means for combating infectious
diseases in the Army. Since
the start of World War II in Europe in 1939, followed by the expansion
of the Army, the
Preventive Medicine Service had seen the necessity for preparing in
advance for dealing with
new and large problems. It was foreseen that there would be urgent need
for the services of the
best civilian specialists in the field of infectious diseases. The
Pneumonia Board of 1918,
previously mentioned, was recalled as an example of the kind of
organization that would be
needed. Proceeding along these lines, Colonel Simmons drew up a plan
for a greatly enlarged
and strengthened civilian body of this type and, on 27 December 1940,
recommended to The
Surgeon General that the plan be forwarded to The Adjutant General for
approval. This was done
the same day by Maj. Gen. James C. Magee, The Surgeon General, and, on
11 January 1941 by
order of the Secretary of War, the Board for the Investigation and
Control of Influenza and Other
Epidemic Diseases in the Army was established. Within a a few months, a
number of civilian
commissions on various infectious diseases were formed, and the
Commission on Influenza was
one of the first to be established. The Board and its commissions were
attached to, and
administered by, the Preventive Medicine Service, Office of the Surgeon
General.

Experience in 1941-42

During the
remainder of the year 1941, the admissions for influenza and the common
respiratory
diseases followed the usual seasonal pattern and fell to the lowest
level in July. However, the
incidence of acute respiratory disease during the summer season
remained higher than the
average for the preceding decade.

With the onset of
open hostilities in December 1941, the mobilization for war was
tremendously
increased. The very rapid induction of men when housing facilities were
inadequate caused
definite overcrowding. It was necessary to reduce the floor space per
man in barracks from 50 to
40 square feet, and a considerable proportion of troops were housed in
tents. Such Housing
conditions undoubtedly contributed to the moderately high admission
rates for acute respiratory
disease in the winter of 1941-42, but no epidemic of influenza was
encountered.

Experience in 1942-43

In the summer of
1942, the military forces were still increasing rapidly. New groups of
recruits
were constantly entering camp, troop movements were

95

continuous, and the expansion
frequently resulted in overcrowding on trains and in barracks,
especially in induction and training centers. There was at the same
time a migration of civilians
into overcrowded industrial centers. In keeping with the recurrence of
influenza A every other
year since 1932, 1942-43 was scheduled for an epidemic with conditions
in the population
apparently favorable to the disease. Studies of vaccination were linked
to this premise, and close
observation was maintained. Influenza A was epidemic in Australia in
May 1942, 18 but
elsewhere the disease did not appear in significant amount, and in the
United States it was not
found.

On the other hand,
noninfluenzal acute respiratory diseases and atypical pneumonia rose to
epidemic heights and maintained a high level throughout the season when
respiratory diseases
were expected to occur. In the continental United States, a peak of 530
per 1,000 per annum for
January 1943 slowly receded over several months. The disease was
particularly prominent in
recruits and in other epidemiologic characteristics differed from the
usual epidemics or
influenza.

Experience in 1943-44

Although influenza
was inconspicuous during the preceding winter, each succeeding season
carried the possibility of a severe epidemic which, with crucial
operations mounting in many
parts of the world, might be critical. Advance information was
desirable. The virus laboratories
of the Commission oil Influenza of the Army Epidemiological Board were
still alert in various
areas, and the continued high incidence of respiratory disease held the
attention of all medical
agencies. Commission investigators identified influenza B widely but
largely subclinically in
two institutions in Michigan during March and April; two cases of type
A were also found.
Sporadic cases of type B were also detected at Fort Custer, Mich., and
among students at the
University of Michigan.19 A small
amount of influenza B was identified in Australia .20

In May, three
sporadic cases of influenza A were identified at Fort Custer, and virus
was
isolated.21 Serologic examination demonstrated that a
limited outbreak in
April among interns in a
New York hospital was influenza A and Eaton detected five cases of
influenza A among students
at the University of California in April and isolated a strain of
virus. Here were striking
evidences of a scattered low-grade circulation of influenza without
epidemic conditions. Epidemic influenza in July was reported in Hawaii
but not iden-

21 Francis, T., Jr.: The
Development of the 1943 Vaccination Study of the Commission on
Influenza. Am. J. Hyg.
42: 1-11, July 1945,

96

tified by type. Scattered flurries in
military camps were observed in Canada.22 In the late spring
and summer, limited scattered bursts of influenza A were identified in
British civilians; 23 in
August a localized unidentified epidemic occurred among United States
troops in Southern Base
Section. Much of the foreign information was only known through
subsequent publication or
through informal channels.

The possibility was
recognized that these episodes might be the forerunner, or first wave,
of a
serious autumnal experience. With plans for evaluation of vaccine by
the Commission on
Influenza actively proceeding, the new strain of virus was incorporated
in the vaccine; the
continuous lookout for influenza was enlarged to include a greater
number of listening posts
maintained by Commission members throughout the nine service commands;
and a formal
arrangement for reporting was concluded. Samplings of throat washings
and blood were
obtained at intervals from patients with upper respiratory disease even
though the diseases did
not resemble influenza clinically. The results from each observation
post were communicated to
each of the others and to the Preventive Medicine Service, Office of
the Surgeon General, at
biweekly intervals.

On 17 and 18
November 1943, several patients presenting a picture which resembled
influenza
were observed in the ASTP (Army Specialized Training Program) unit at
the University of
Michigan. Throat washings given to ferrets elicited a typical reaction,
and transfer of ferret
material to eggs permitted identification of influenza virus, type A.
On 22 November, Dr. E. R.
Rickard in St. Louis, Mo., reported that between 11 and 18 November
what appeared to be an
epidemic of influenza had occurred in the ASTP unit at St. Louis
University, involving 100 out
of 550 men. He also reported that in one of the groups under
observation at the University of
Minnesota at Minneapolis, a sudden outburst of 20 cases had occurred on
21 November. Type A
influenza virus was identified by direct inoculation of throat washings
into the allantoic sac of
eggs. All other investigating groups were notified that influenza A had
been identified in both
the Sixth and Seventh Service Commands.

Word was received
from Lt. Col. F. B. Lusk, MC, Chief, Medical Service, Station Hospital,
Fort
Custer, on 15 November 1943, that a sharp increase of febrile
respiratory disease had taken
place. Material obtained from patients becoming ill there during the
next week demonstrated
that almost all of these patients had influenza A. After this time the
spread of the disease was
rapid, and subsequent reports from Commission members indicated that,
within 7 to 10 days,
cases had begun to appear over a great part of the United States.

From July 1943 to
the week ending 6 November 1943, the weekly rates for influenza and
common cold for the entire Army in the continental United

22 Hare, R., Hamilton, J., and
Feasby, W. R.: Influenza and Similar Respiratory Infections in a
Military Camp over a
Period of Three Years. Canad. J. Pub. Health 34: 453-464, October 1943.

States had remained at a level of
approximately 100 per 1,000 per annum and up to 30 October
in none of the service commands had rates reached 150.

In the week ending 6
November 1943, the first rises to levels greater than 150 were noted in
the
Sixth and Seventh Service Commands, to greater than 200 in the weeks
ending 13 and 20
November, respectively; the two areas proceeded rapidly to reach their
respective peaks of 1,279
and 1,050 the week ending 4 December (table 19). The first sharp
increase recorded at posts in
these commands was at Fort Custer where rates rose from 113 in the week
ending 30 October to
441, 1,075, and 1,212 in the weeks of 6, 13, and 20 November,
respectively. It was here, too, that
influenza A was identified in May 1943. The First, Second, Third, and
Fifth Service Commands
reached heights of greater than 200 during the week ending 27 November
and attained their
peaks the week of 11 December. Rates in the Fourth, Eighth, and Ninth
Service Commands,
although giving evidence of increased prevalence of influenza, did not
exceed 200 until the week
of 4 December. The peaks in these three commands were considerably
lower and later in their
occurrence than elsewhere.

It is of interest
to note that on 24 November, at which time the recorded figures give
little
indication of influenza in the Eighth Service Command, patients with
influenza A were
identified in the station hospital at Fort Custer. These men had
entrained 48 hours earlier in
Texas (located in the Eighth

98

Service Command) and lead remained in the troop train but became ill
before arrival at Fort
Custer.

The highest rates
for the entire Army in the continental United States were 631 and 593
in the
weeks of 11 and 18 December. By 7 January 1944, the epidemic period had
practically ended in
all areas, and the rate for the entire Army fell below that for the
previous year but, due to the
seasonal increase in upper respiratory infection of other etiology, in
no command did the rate
return to the level which had existed in early November. That the
continued incidence was not
due to influenza A is seen in the reports of the different
investigators who, with the exception of
those in California, considered the epidemic prevalence of cases to
have ended before 1 January.
Further support for this conclusion is found in the results of studies
made in the respiratory
wards at Fort Custer on 28 January 1944 when serologic tests in recent
febrile respiratory
admissions were all negative for influenza A although similar studies
on 20 November and 27
December were almost uniformly positive. Precise information of the
epidemic is largely derived
from the Commission studies.24

In an analysis of
the reported cases of influenza during the 1943-44 epidemic among the
civilian
population, Holland and Collies 25 found that the maximal
incidence of
the disease for the
country as a whole occurred between 25 December 1943 and 4 January
1944, 2 to 3 weeks later
than that noted in the Army. They conclude that the 1943-44 epidemic
was larger than any since the period 1918-20" For a group of 90
large cities, the excess mortality during the 11 weeks from 21 November
1943 to 5 February 1944 was 50 per 100,00 population in
comparison with 65 per 100,00 for the epideic of 1928-29 and 598 for
the pandemic of 1918-19. Comparable data are not available for
the 1936-37 epidemic, but a statement has been made that it wa smaller
than earlier outbreaks.

Collins 26 compared
the results of house-to-house canvasses in Baltimore during the 1943-44
epidemic with those in other communities during 12 other epidemics
since the beginning of 1918. He states, "considering actcual
rates, the recorded incidence for all ages in the 1943-44 outbreak was
higher than in any other epidemic since that of 1918-19; the incidence
among children under 10 years of age approximated that in 1918-19, and
the incidence above 40

years was greater than in 1918-19. The percentage of the total cases
that were complicatd by
pneumonia in the 1943-44 epidemic was far below the figure for any
other epidemic for which
data are available." Nevertheless, the pneumonia rates among persons
over 25 years of age
correspond closely to those recorded in this age group during the
epidemic of 1928-29.

The data from all
sources indicate, then, an epidemic of high incidence making its
earliest
prominent appearance in the North Central States in the first half of
November 1943, spreading
rapidly to a peak in December, and then promptly declining to the
seasonal level of respiratory
disease, thereby occupying a total of approximately 6 weeks for the
evident epidemic period. It
is of interest that, in the Gulf, Southwestern and Pacific States, the
onset was slower and the
peak lower and later than in other parts of the country. The data
indicated that in terms of
incidence the outbreak was of major proportions but the complications
and case fatality rates
were low, although its effect on total mortality by virtue of the high
incidence was greater than
the case fatality rate would indicate.

In the entire
Army, only 8 deaths occurred among influenza patients and 290 deaths
among
admissions for pneumonia oter than primary atypical. Even a rough
estimate of case fatality
rates is unreliable since reported and summarized data are inconsitent.
Of the total 89,764 cases
recorded for the total Army in 1943, 69,840 were in the United States
with 5 deaths and a case
fatality rate of 0.01 percent. In the European theater, 4,717 cases are
recorded with 1 death
(table 20).

European
Theater of Operations.-American troops in the European theater
experienced an
epidemic of influenza A in the fall of 1943, which reached its peak
about 2 weeks earlier than in
the United States. 27 After a suggestive
rise in reported cases of acute respiratory disease in the
last week of October and the first week of November, there was an
extremely rapid incrase to
maximum annual admission rates of 1,079 per 1,000 strength for the week
26 November 1943. The decline of the epidemic was as sharply marked as
its rise. By the end of December, the rate
was 387. Virus A was demonstrated to be present in each of the
principal base sections by
serologic studies. Influenza B was not found. The disease was described
as mild and
uncomplicated with an acute onset and lasting only a few days.
Constitutional rather than local
symptoms predominated. The outbreak was almost completely unassociated
with an increase
prevalence of primary and secondary penumonia. There were no death.

According to
Gordon, admission rates for common respiratory diseases, including
influenza,
among Negro troops were much less than for white troops in the theater.
The maximum rate for
the two groups occurred during the week of 26 November 1943. The rate
for white troops was 1,
129 and for Negro troops, 477.

27 Gordon, John E.: A History
of Preventive Medicine in the European Theater of Operations, U.S.
Army, 1941-45,
vol. I. (Official record.)

The civilian
population of the United Kingdom had a similary epidemic at
approximately the
same time.28
It differed from that of the
United States Army principally in respect to mortality. The maximum
number of 1,148 deaths from influenza was reported during the week of
11
December 1943. This was 2 weeks later than the peak for the
military cases. The deaths were
largely among the older age group.

Other overseas theaters. -Alaska
reported an explosive epidemic suggestive of influenza
among military and civilian populations in the first 2 weeks of April
1943, and, again beginning
on 21 December 1943, there was a sudden increase in the incidence of
acute respiratory disease
at Fort Greely, Alaska, which quickly reached a peak and subsided
within 1 month. Small
outposts were not involved. A total of 535 cases were admitted to
hospital and 1,043 to quarters. Average duration of hospital and
quarters stay was 5 and 4 days, respectively. The clinical
description was "typcal" of influenza. There was no recurrence and no
deaths.

Dr. J. H. Dingle,
a member of the Commission on Acute Respiratory Diseases, investigated
a
mild epidemic of influenza that occurred in Puerto

28 See
footnote 23, p. 96.

101

Rico in July 1943. It was
estimated that 500 cases occurred among the civilian population of
San Juan. There was no pulmonary involvement. Troops in Saint Thomas
had a small outbreak
of approximately 50 cases.

During July and
August, an epidemic of acute respiratory disease, probably influenza,
occurred
in the 65th Infantry Division (Puerto Rican Regiment) with
441 admissions. There were 452
cases among employees of the Panama Engineer Division. Cases were also
reported in Camps
Sabanita and Coiner, Canal Zone.

Hawaii reported an
epidemic of mild influenza in late June and July.

In the Southwest
Pacific and China-Burma-India theater no influenza outbreak were
reported.

In the North
African theater, especially in Italy, no evidence of influenza in
significant amount
was discerned.

Variations in behavior. -The
commission on Influenza reported that differences in the
behavior of the epidemic in adjacent units were clearly observed. For
example, at the University
of Minnesota, the incidence among the total study population was 5.9
percent, while in another
group it was 38 percent. At the University of Michigan, a wide
variation in involvement of
different companies of the ASTP unit was observed, two companies having
but a single
hospitalized case each, while from another company not in the study 20
percent were
hospitalized. The commission on Acute Respiratory Diseases had recorded
a number of
significant features. At Camp Mackall, N.C., the troops were all
seasoned men with 6 months or
more of training. The epidemic appeared in all parts of the camp in an
explosive fashion with 64
percent of the admissions occurring in a period of 5 days.
Approximately half the admissions in
the 11th Airborne Division occurred among the artillerymen with a rate
of 8.8 percent, which
comprised less than one-fifth the total strength. Very low admission
rates, approximately 1.0
percent, were observed among 2 of the 3 infantry regiments. It was
thought that "the
explosiveness and short duration of the epidemic at Camp Mackall appear
to be related to the
environment and activities of the troops. There was marked crowding in
the barracks; the
inhabited area of the post was small; and all groops shared common
transportation facilities." At
this camp, 29 cases of pneumococcal pneumonia, most of which were type
I, occurred during the
epidemic period with a rather prompt disappearance thereafter.

At Pope Field,
Fort Bragg, N.C., a detachment of glider mechanics had sick men with
them on
arrival at the post. They were put into quarantine under crowded
conditions and in 7 days had a
total admission rate of 35 percent. The remainder of the units in
adjacent barracks had no
contact with the affected unit. Cases occurred over a month's time with
a total admission rate of
5 percent. A contrasting episode was that of the 326th
Glider infantry Regiment which arrived by
train from the Midwest; a large number of admissions occurred in the
first 2 days, but then the
incidence dropped and remained low as they were moved into uncrowded
barracks and field
activities. No explosive outbreaks were seen at Fort Bragg in troops
engaged in continuous

102

field training. These reports emphasized, too, that at Fort Bragg
the virus was repeatedly
introduced by men who had acquired their infection in widely separated
areas of the country. This was also noted at Fort Custer where troops
arriving promptly from Texas were sick
although the disease had not been recognized there.

Gordon refers to the
unified experience of the 358th and 360th
Engineer (GS) Regiments, old
units which constituted a single military population. The epidemic
began 8 November and
reached the extremely high level of 6,111 per 1,000 per annum during
the week of 26 November. The disease declined rapidly without
fatality. This represents again the abrupt rapid involvement
of seasoned troops with a mild disease. The apparent spread from unit
to unit and the
irregularity in incidence of adjacent units is illustrated in the
following example from the
European theater.

General Depot G-18
of the Western Base Section had a strength of 5,737 men divided into
eight camps. The first
five were situated near Sudbury, England, and Nos. 6, 7, and 8 were at
Eggerton, several miles away. On 3
November, the first probable patient with influenza from C Company,
131st
Quartermaster Regiment (TRK), Camp
No. 2, reported to the dispensary with headache, backache, prostration,
and an elevated temperature. Within 12
hours, the medical officer developed the same symptoms. The following
day 21 men of C Company were ill. On
5 November cases began to develop in the 445th Engineer Base Company,
on 7 November in 608th Engineer Light Equipment Company and on 8
November
in the 887th Ordinance Ammunition
Company. Altogether, Camp No. 2 with 837 men had 121 patients in
hospital with influenza, practically all of
whom developed the infection between the 4th and 11 of November and
belonged to one or other of the four
companies noted.

Camp No. 1 was
located in the same vicinity as Comp No. 2, and shared the same
dispensary. The outbreak in this
camp extended over the same period. Of 849 men, 72 were admitted to
hospital with influenza.

Camp No. 3,
housing the 534th Quartermaster Service Battalion, a colored labor
unit, had no known association with
any other camp except for an exchange of labor with the 2d platoon of D
Company located at Camp No. 8. The
outbreak of influenza began at Camp No. 3 on 14 November with the
hospitalization of six men. The following day
so many new cases appeared that two empty barracks were converted into
a camp infirmary. During the period 14 to
24 November, this unit had 111 cases of respiratory disease. The
infection spread to 2d platoon, D Company at
Camp No. 8 and 26 cases were reported between the 22d and 25th of
November. With the exception of this platoon
there were few cases of respiratory infection at Camp No. 8.

Camp 4, with 689 men, sent
15 to the hospital between 17 November and 25 November, and the daily
sick call
averaged about 15 which was only slightly higher than had held in
October.

Camp 5, an Air
Corps Depot having little association with other camps, had no cases of
influenza.

Camps 6 and 7, located
several miles from the other camps, likewise had very few cases of
respiratory disease.

It is clearly
demonstrated that respiratory disease spread rapidly from one group to
another within an incubation
period of about 24 to 48 hours. Association of groups was a much more
important factor than kind of work or type
of quarters.

It was recognized
from the start that the epidemic disease affected recruits and seasoned
men
alike. In fact, at many posts this feature was

103

emphasized to differentiate between
influenza and the acute respiratory disease which was
preponderant in recruits. At Fort Bragg, it was precisely observed that
the incidence of influenza
A was not different among the two classes of men living under
comparable conditions. This
may well be indicative of the fact that infection with influenza is not
a year-in, year-out process
but one which takes place primarily in epidemic periods; alternatively
it may also be interpreted
to demonstrate that immunity is not durable or that strain variation is
involved.

As previously
mentioned, in the European theater the peak incidence of influenza in
Negro
troops was less than half that in white troops. No other data of this
nature are available.

In reviewing the
variations that were encountered, it becomes increasingly convincing
that, apart
from the need for exposure of susceptibles to disease, the most
important factor in determining
the behavior of epidemic influenza within limited units is that of
crowding, particularly when a
high rate of change in the population exists.

A few instances are
recorded of the epidemic moving into units in which beta hemolytic
streptococcal infection was prevalent.29 The
incidence of respiratory diseases was highest
thoughout the epidemic in the Seventh Service Command, where
streptococcal disease was
highly prevalent. There was in these areas, however, no evidence that
the bacterial invasion was
accentuated by influenza as was clearly the case in 1918. Coburn 30
has indicated that influenza
had a definite influence upon the behavior of streptococcal infection
in naval units, and, at the
United States Naval Training Center at Farragut, Idaho, the occurrence
of influenza was clearly
related to an exaggeration in spread and severity of streptococcal
disease. There are also
numerous studies indicating that pneumococcal penumonia was more
prevalent during the
epidemic, but in other instances as at Sioux Falls, S. Dak., where
pneumonia was epidemic,
Hodges and MacLeod 31 conclude that
influenza was not unduly prominent as a participating
factor.

Special concern
was attached to the transport of troops during the epidemic. Serious
trouble was
not encountered in overseas movements although a convoy of 63,750
troops had 7,529 (12
percent) sick calls for respiratory disease while en route to Great
Britain inDecember; 962 men
were hospitalized and 86 were evacuated to hospital on debarkation.32
In another instance, 23
percent of a contingent were sick aboard ship. Official recommendation
was made that at all
ports of embarkation a minimum of 60 square feet housing space be re-

29 See footnote 24 (2) and (3), p. 98.

30
Coburn, A.F.: Mass
Chemoprophylasix. Th U.S. Navy's Six Months' Program for the Control of
Streptococcal
Infections. In United States Navy Department, Bureau of
Medicine and Surgery: The Prevention of Respiratory
Tract Bacterial Infections by Sulfadiazine Prophylaxis in the United
States Navy. Washington: U.S. Government
Printing Office, 1944, pp. 149-162.

quired; this was an effort to avoid
crowding and illness at the time of embarkation. 33

Control measures. - The general
control measures were those designed to prevent or retard the
spread of infection from person to person. Emphasis was placed on the
avoidance of
overcrowding by increasing the floor space per man in barracks and
reducing the number of
troops per car on trains. Troop movements were kept at a minimum during
the outbreak. Personal hygiene and proper sterilization of messgear
were stressed. During the epidemic,
fatigue and exposure to cold and wetness were minimized. In
high-priority units, medical
inspection of troops and the hospitalization of patients with incipient
disease were advocated.

The action taken
by the Preventive Medicine Service of the Surgeon General's Office to
maintain close touch with the epidemic situation and to gain the
advantage of environmental
control measure is summarized as follows: 34

1. The first
definite information that epidemic influenza was occurring came on 21
November
1943. The isolation of virus A from such an outbreak was first reported
on 25 November.

2. On 3
December, the Medical Statistics Division was requested to furnish the
number of cases
of influenza separate from common respiratory diseases.

3. All service
commands, the Air Surgeon, and the Chief of Transportation were
requested on 6
December to notify all stations under their jurisdiction to report by
telegram all influenza
outbreaks then occurring, as well as future outbreaks, to The Surgeon
General. This action was
taken at the request of General Simmons, and the reports were rendered
under previously granted
Control Approval Symbol MCE-64.

4. On 16
December, all posts over 5,000 strength were asked to telegraph weekly
reports of the
number of cases of common respiratory disease, including influenza and
pneumonia, to service
command headquarters, which was in turn, to forward a consolidated
report by wire to The
Surgeon General. This action followed a staff conference at which it
was indicated that The
Surgeon General was expected to know the current situation with respect
to influenza. The
reporting system thus set up reduced by a week the delay in compilation
of rates, although the
rates computed were, of course, estimates based on a sample only.
Experience showed the
estimated rates to be fairly accurate in comparison with the final
returns on the monthly
summary reports from all posts.

5. A report based on
the telegraphic rates was made by The Surgeon General to the Secretary
of
War, Chief of Staff, and Commanding General,

33 (1) Coded message (routine), Chief of
Transporation to all Ports of Embarkation, 19 Dec. 1943, subject:
Instructions in Control Measures to Be Put Into Effect. (2) Memorandum,
Chief of Staff for Commanding General,
Army Service Forces, 30 Dec. 1943, subject: Considerations of Influenza
Precautions With Respect to Overseas
Troop Movements. (This was accompanied by a list of 15 stations
designated to provide overflow capacity for
regular port staging areas in an emergency.) (3) Momorandum, Commanding
General, Army Service Forces, for
Chief of Transportation, 6 Jan. 1944, subject: Measures to Prevent
Epidemics During Troop Movements.

ASF (Army Service
Forces),
on 21 December, and similar reports were rendered

at the
end of the
month and again
on 7 January 1944.

6. On 28

December, a request was made to
the Control Division, ASF, for approval of the weekly telegraphic
report;
it had previously been understood that such approval was unnecessary.
This request was disapproved, and The
Surgeon General was instructed to advise service commands immediately
that the

weekly telegraphic report was no
longer required. The Preventive Medicine Service, Office of the Surgeon
General, informed the Commanding
General, ASF, that his instructions had been carried out but indicated
that this office did not concur in the objections
to the report.

7. All
service commands, the Air Surgeon, and the Chief of Transportation were
notified by wire on 7 January

1944
that the telegraphic reports of respiratory diseases were discontinued.

8. On 15
December 1943, the Deputy Chief of Staff sent a radiogram to all major
commands in the United States
calling attention to control measures and authorizing hospitalization

of civilians in military hospitals when
necessary. Reference was made to the maintenance of production
schedules in industrial plants. Reports of influenza
outbreaks in units soon to go overseas were to be telegraphed to The
Surgeon General.

9. On 19
December, the Transportation Corps telegraphed all ports, giving
instructions in control measures. These
instructions were prepared in consultation with the Epidemiology
Branch, Preventive Medicine Division, Office of
the Surgeon General.

10. On
30 December 1943, the Chief of Staff sent the Commanding General, ASF,
a memorandum, entitled
"Consideration of Influenza Precautions With Respect to Overseas Troop
Movements," accompanied by a list of 15
stations designated to provide overflow capacity for regular port
staging areas in an emergency.

11. The
Commanding General, ASF, in his memorandum for the Chief of
Transportation, dated 6 January 1944,
entitled "Measures to Prevent Epidemics During Troop Movements,"
forwarded a copy of the memorandum from
the Chief of Staff, previously referred to.

12. The Commanding General, ASF, also sent The Surgeon General a
memorandum, same subject, on 6 January,
including a copy of the memorandum from the Chief of Staff and attached
list of stations. The Surgeon General was
directed to issue necessary technical instructions and report
recommendations for the modification of present
procedures. The Surgeon General's endorsement on 20 January stated that
an article on influenza would be published
shortly in a medical technical bulletin and recommended that directives
be published requiring a minimum of 60
square feet of space per man in barracks.

13. The Chief, Preventive Medicine Service, Office of the Surgeon
General, sent a draft of medical technical bulletin
entitled "Influenza," to the Executive Officer on 28 January.

14. On
29 January, a directive entitled "Measures to Prevent Epidemics of
Respiratory Diseases," was sent to all
defense commands, service commands,

106

ports, and technical
services. This was substantially the same as the letter recommended by
The Surgeon General.

Cooperation
with civilian groups.-Because of the potentialities of a severe
outbreak of influenza similar to the
1918-19 epidemic, plans were made by the Preventive Medicine Service,
Office of the Surgeon General, for the
Army to give assistance in the medical care of civilians in cases of
emergency. Medical Department personnel,
supplies, hospitalization, and transportation were to be made available
to the maximum extent after the first and
second echelon facilities consisting of the local and State
physicians and facilities, American Red Cross, United
States Public Health Service, and Office of Civilian Defense, were
exhausted. Hospitalization of civilian personnel
was authorized, and each service command and post surgeon made plans to
be put into effect if indicated. As the
epidemic remained generally mild, these procedures were not used.

Experience
in 1944

With the
abrupt subsidence of the epidemic of influenza A in the winter of
1943-44, the admission rates for
respiratory diseases within the continental limits of the United States
continued to decline rapidly and remained
below the average level of Army experience for the decade 1930-39
(chart 13). After January, they also readied a
level well below that of the three preceding winters. The Army at this
time was composed largely of seasoned
troops since the rate of induction was low as compared with the 3
preceding years.

Experience in 1945

A small
seasonal rise in rates occurred during the winter months 1944-45 but
that for troops in the United States
remained under 200 admissions per 1,000 per annum. The overseas
theaters had similar low rates for acute
respiratory disease. No outbreaks of influenza occurred. However, the
Commission on Influenza continued a more
extended alert for detection by investigating unusual rises in
admissions for acute respiratory disease and sampling
cases in respiratory, wards of various Army hospitals. Investigation of
an outbreak of illness in the Antilles
Department reported to be influenza revealed it to be infectious
mononucleosis; nevertheless, an opportunity was
provided for setting up a center for the identification of influenza in
the area.35

Beginning
in March 1945, small localized outbreaks of influenza B occurred in
many parts of the United States and
overseas theaters. Detailed investigations of a number of these
outbreaks are described in special reports from
members of the Commission on Influenza to The Surgeon General, United
States Army. However, it is of interest
and importance to indicate the time, location, and extreme variability
of these widely scattered upsurges of the
disease which were identified by virus isolation or by serologic
evidence.

The earliest outbreak occurred in March at
Sioux Falls, although the serologic evidence of influenza B was not
obtained until after the virus had been identified by Dr. J. E. Salk in
sharp outbreaks at Buckley and Lowry Fields,
Colo., in May. Streptococcal infection was also high. Evidence pointed
to the fact that influenza was present, too, in
the neighboring civilian population of Colorado as a very mild illness,
not recognized clinically as influenza.
Serologic. studies at this same time in a hospital ward for respiratory
illnesses at Sheppard Field, Tex., demonstrated
that influenza B was present although its nature had not been suspected
clinically. In April, a flurry was identified
serologically at Fort Lewis, Wash., by the Ninth Service Command
Laboratory. A sharp civilian outbreak in the
town of Kasson, Minn., was recognized only in the school children, 80
percent of whom were affected; the peak was
in the middle of May. Tests with sera from patients convalescent from
an outbreak in Alaska in May demonstrated
influenza B.

In June and
July, sharp outbreaks occurred in the prisoner-of-war camps at Camp
Edwards, Mass., and Camp
Atterbury, Ind. The Fifth Service Command Laboratory identified the
Camp Atterbury outbreak. The outbreaks
seemed to be limited entirely to the prisoner-of-war compounds with
prevalence of 10 to 12 percent, but Dr. 'I'. P.
Magill demonstrated by serologic studies that infection had been widely
distributed in United States military
personnel at Camp Edwards. He suggested that the Americans were being
largely immunized by subclinical
infection and that the prisoner groups became more prominently affected

if they were not closely associated with
United States troops. The Antilles Department laboratory reported an
epidemic in San Juan beginning 8 June and
reaching a peak about 22 June. In Jamaica, an estimated 50 percent of
the population of Kingston were attacked in
an epidemic. The disease was also identified in United States Army
troops in Panama and in civilian employees in
the Canal Zone. It is well to point out that Army laboratories
were at this time actively engaged in the detection of
the disease both by virus isolation and serologic tests.

Influenza was
widely disseminated over a great part of the Pacific area. In Honolulu,
a sharp civilian epidemic of
7,000 to 8,000 cases was reported by the Board of Health from 1 June to
15 July. Army admissions at this same
time increased sharply with a peak on 27 June. The author and Capt. G.
K. Hirst, MC, undertook an investigation at
this time in the Pacific Ocean Area. Sampling of cases showed virus B
was widespread. In this instance, too,
streptococcal infection was prevalent without serious complications.
Vaccination of essential personnel was carried
out. The disease was demonstrated in naval forces at the same time, and
vaccination was extended to certain
specific personnel. At Tarawa in June, 83 percent of the Gilbert-Ellice
labor troops were affected in an epidemic that
followed the arrival of two Army ships. Caucasians in the area had
little illness. Judged by admissions, little
respiratory infection

occurred at Saipan and Guam, but
serologic samplings showed influenza B to be prevalent. On
Okinawa, serologic studies of a denguelike

108

disease that was prevalent among the troops showed some
significant rises in titer for influenza B from 23 July to as
late as 27 August.

In July,
evidence accumulated of localized outbreaks
in Australia 36 and British Guiana. 37
In California, influenza B
was identified by Dr. M. D. Eaton in troops who became ill aboard
transports from the Pacific, and, at the same time,
a local outbreak was seen at Stockton Ordnance Depot.

From late
August through October, influenza B was encountered at Fort Bragg, Fort
Dix, Fort Lewis, and at Fort
Benjamin Harrison, Ind. In October, Burnet reported both influenza A
and B in Australia with a concentration of
cases in young people or in country districts while troops and adult
city dwellers escaped almost completely. He
reported two patients with influenza from whom virus B was isolated; 10
to 12 days later, during a second attack,
virus A was also isolated from those individuals.

The
disease was mild during the summer of 1945 but varied from typical
febrile illness of 3 to 4 days' duration, with
an occasional instance of pulmonary involvement, to transient
indisposition and subclinical infection. It is quite
likely that in the civilian population much more of the disease was
unrecognized and ignored. However, the
accumulated information identified clearly a continued but shifting
prevalence of influenza B during a period of 8
months. The alerted interest was thus very effective in demonstrating a
peculiar, irregular blustering occurrence,
rising here or there for many months. Some of the minor episodes were
of considerable size but localized, yet they
recurred in the same posts at intervals of months in a typical
endemic-epidemic manner.

The
extensive distribution of the disease was considered to indicate that a
definite epidemic wave was likely in the
latter part of the year. On this basis, the Commission on Influenza
recommended to General Simmons, on 21 June
1945, that vaccination with influenza A and B be carried out in the
entire United States Army during the month of
October 1945. War Department Circular No. 267, dated 5 September 1945,
instructed that the forces in all Army
commands be vaccinated in October and November.

The
anticipated epidemic of influenza B occurred in November and December
1945. A definite increase in
respiratory admissions in the Army in the United States began in the
week ending 23 November when the rate rose
from 88 to 103. It rose to 148 the following week and continued to a
peak of 170 in the week ending 14 December. This rise was strikingly
similar in time to the onset of the 1943 epidemic of influenza A.
However, the increase was
not nearly so great or abrupt.

The
civilian population of the United States experienced an epidemic at the
same time. Reported cases rose abruptly
beginning the last week in November and reached a sharp peak of 148,688
cases during the second week

in December.38They fell
rapidly in the next 3 weeks to less than 50,000 cases per week. The
areas most severely
affected were the South Atlantic, South Central, East North Central,
and Mountain States. The Pacific and New
England areas, which were not affected severely, reached peaks late in
December or in the first 2 weeks of
January.In comparison with the 1943-44 epidemic of influenza A, the
1945-46 epidemic of type B in the general
population reached a higher level for the peak week, but in total cases
it was less. For the period 18 November 1945
to 26 January 1946, a total of 454,833 cases were reported ill the
States where influenza is a reportable disease. For
the corresponding period in 1943-44, there were 587,193
cases and in the nonepidemic year 1944-45 only 32,620
cases. In the peak week of December 1945, the State of Kentucky
contributed 60 percent of the total cases while
this same State contributed 18 percent in the 1943-44 peak. This report
is apparently made on the basis of estimates
rather than actual reported cases. If the estimates for this State were
excluded for comparison purposes, the civilian
incidence in 1945-46 was at least half of the 1943-44 epidemic.39

In the
Army, the increase as measured by admission rates for respiratory
diseases, after correction of strengths due to
the number of troops on furlough during this period, remained less than
25 percent of the 1943-44 epidemic; the
actual increase over the preepidemic level was so small as to give
evidence of only a minor increase. The Navy
admission rates were 55 percent of those in 1943-44. In
attempting to evaluate the efficacy of the vaccine, a detailed
study of the incidence in the Army and Navy was made. The evidence
available indicated that vaccination played a
considerable role in the reduction of influenza in the Army (luring the
winter 1945-46. More specific studies in the
comparison of ASTP units with naval and civilian students at
universities are given under the vaccination studies.

In England
and Western Europe, the possibility of a widespread influenza epidemic
appeared as a serious threat in
the fall of 1945. The shortage of fuel, the nutritional status of the
population, and the continued shifting and
crowding of displaced persons on the Continent appeared to set the
stage for such an occurrence. In order to
establish listening posts and to organize laboratories for the
detection of influenza, a mission consisting of Dr. Salk,
Maj. G. J. Dammin, MC, and Lt. V. Sprague, MC, was dispatched to the
European theater in November 1945.40 Countrywide epidemics of mild influenza
B were reported in December in Belgium and Holland.41
Sporadic cases
of influenza A and B were identified in United States troops and
civilians in Germany, but no general epidemic
occurred. A continuous survey center for the area was established in
the Fourth Medical General Laboratory. In

38
Prevalence of Disease in the United States. Pub. Health Reps. 60 and
61, July-December 1945 and January-June
1946, respectively.

England, there were few sharp
outbreaks recognized, but influenza B was identified in most areas with
the height of
the prevalence in January 1946. As measured by an increase
in deaths, the epidemic was considered moderately
severe.

The Army had
essentially completed its year long experience with influenza B by the
end of 1945, although some
extension into 1946 was noted in Europe. It is of interest, however, to
note that troops, mostly from the 13th
Replacement Depot in Hawaii, had a sharp increase of respiratory
disease about 1 February 1946, which was
identified serologically as influenza A.42
In the remainder of the Army, respiratory disease reached a point
comparable to the same period of 1945, the lowest recorded level for
the season (chart 13). The Army was being
demobilized, and the threat of influenza which had hung over the entire
period of World War II was dispelled. The
experience of 1918 was not renewed, and influenza again behaved as a
disease not primarily related to military
conditions.

The
tremendous dislocations of populations, the destruction of housing, and
the rapid intermingling of people from
many areas under crowded conditions was a milieu in which epidemics of
typhoid fever, diphtheria, and tuberculosis
rapidly gathered momentum. Circumstances were such that influenza
comparable in severity to that of 1918 would
be insusceptible to control. No other conclusion seems possible but
that the biology of the infectious agents was the
decisive factor in avoiding such an event. The studies of the disease
and its prevention contributed greatly to a better
understanding of its epidemiology and were responsible in a significant
fashion for heightened efforts to identify and
control respiratory disease of all types. There was, as always, a
somewhat fatalistic attitude toward prevention or
control measures, but in many situations a true effort was made to gain
what benefit could be had by early institution
of measures to limit crowding, to control transport of infected men,
and at times to use sulfonamides
prophylactically in the hope of reducing complications.

Circumstances
were favorable. The periods of greatest effort were largely free from
influenza or the disease was of
sufficiently mild character to avoid serious disturbance. The
widespread epidemic of 1943 was not prevalent in the
major combat area at that time, Italy. In 1945, the European theater
was essentially free from influenza B. Reports
from the Pacific theater contained no significant references to
influenza until 1945, with the exception of Hawaii
which appears to have become a major crossroads for the transfer of
influenza. Other theaters in the Far East made
no reference to the disease. There is little doubt that the mild
character of influenza in busy areas attracted little
attention, and many were concerned with a diagnosis of influenza only
if it were rapidly fatal or overwhelming. In
many instances, epidemics clearly shown to be influenza, with classical
clinical and epidemiologic

characteristics, were called
nasopharyngitis. This practice sometimes avoided additional
requirements imposed by
the diagnosis of influenza. The constant insistence of the

Preventive
Medicine Service, Office of the Surgeon
General, and its expert consultants on prompt investigation of
outbreaks had left little doubt that the early
distribution of information was an important factor in maintaining the
alertness and interest of all commands.

RESEARCH
WITH INFLUENZA
VIRUS

Development
of Knowledge

The lack of
decisive information regarding the etiology of the pandemic disease of
1918 led to numerous efforts to
establish the nature of the inciting agent of influenza. Various
bacterial agents were isolated, heralded, and
dismissed. Shope, in 1931,43 however,
described and established the evidence that swine influenza is caused
by a
combined infection of virus and Hemophilus influenzae suis,
with the former serving as the effective agency in
dissemination and immunity. The parallelism between the characteristics
of this disease in swine and influenza in
men, together with an etiologic complex to mollify the
bacterial and viral schools of thought, promptly opened the
field to further work. At the same time, viral studies of the common
cold and psittacosis were enhancing interest in
respiratory diseases.

Type A virus.- In 1933, Smith,
Andrewes, and Laidlaw44 isolated a virus from human cases of
influenza
A, which
produced in ferrets, inoculated in the nose with garglings of the
patients, a simple febrile upper respiratory disease of
3 to 4 days' duration involving the turbinate tissues. After recovery
they were resistant

and developed in their blood
antibodies which would neutralize the virus so as to prevent infection
when a mixture of convalescent serum and
virus was inoculated into normal ferrets. In 1934-35, the author45
Confirmed and extended those results with
recovery of virus from influenza patients in many communities of the
Western Hemisphere, and also in showing
that, with repeated passages of these human strains in ferrets by
intranasal route, the animals developed extensive,
fatal viral pneumonia. Virus was established by intranasal inoculation
in mice so as to produce fatal viral
pneumonia. Through their use, neutralization tests for antibody were
readily possible. Complement fixation tests
were developed. Virus was cultivated ill tissue culture and in chick
embryos.46 Subsequently, the observation by

Hirst,47 and McClelland and Hare,48
that avian erythrocytes were agglutinated by influenza
virus in infected
allantoic fluid, added another important technique for identification
of virus and serologic diagnosis. The application
of these procedures to the problem of epidemic influenza became
progressively established in a few years.49

It was found
that, after the first years of life, a large proportion of the human
population had antibodies to influenza
A virus. Hence, at the onset of illness, a patient might well possess
demonstrable antibodies from earlier infection,
but, with recovery, a sharp rise in the level took place. It was
necessary, therefore, for specific diagnosis to compare
the titers of antibody in the acute phase of illness with that reached
in convalescence. The specificity of the reaction
was also clearly established. The serologic test thus became a
procedure applicable to clinical diagnosis and to
broader epidemiologic investigation in conjunction with the, isolation
and identification of virus.50

Employing
these procedures, it was shown that outbreaks associated with type A
virus lead recurred at intervals of 2
years between 1932 and 1940-41.51
They varied widely in extent and severity; the 1936-37 epidemic was
worldwide and that of 1938-39 extremely spotty and of low order, but
they were both influenza A. That not all the
strains of influenza A are identical was established in 1936; 52 while
most strains from the same epidemic are
closely similar, those from different epidemics may show
distinct differences. That they are of the same type can be
demonstrated by complement fixation or by hyperimmunization of animals
which bring out the common type
antigenicity. Under the latter circumstances, the swine strains were
also seen to be related to type A strains from
man. Nevertheless, another feature arose to be considered in
recurrences of influenza.

Type B virus.- From the epidemic in
the early months of 1940, another influenza virus, type B, (p.90) was
established, and it was then possible to demonstrate that the
widespread epidemic of 1935-36 was also influenza B.
This virus was shown to be immunologically distinct from type A,
thereby introducing a second disease, clinically
and epidemiologically influenza, to be considered in the analysis of
recurrences and of immunity to influenza.

disease of man.53
Hemophilus influenzae was uncommon, but, in occasional,
rapidly fatal cases with extensive
destruction of the respiratory epithelium, hemolytic Staphylococcus
aureus had been encountered. Thus, the
evidence firmly established influenza virus as the essential infectious
agent in characteristic epidemic influenza.

Antibody formation. Influenza virus
produces all infection essentially limited to the respiratory tract. It
has a
highly selective, destructive action upon the ciliated respiratory
epithelium of the nasal mucosa and upon that of the
trachea and bronchi. After large doses given intraperitoneally to mice,

virus can be recovered from the lungs and, if
well adapted to that species, may produce extensive pulmonary lesions.
The WS strain of type A can be established
ill the central nervous system of mice by the intracerebral route.
Generally, however, the influenza virus can be
considered rather strictly pneumotropic since, under most
circumstances, inoculation of various species with active
virus by other than the respiratory route elicits no evidence of
infection but, circulating antibodies and resistance
may ensue.

Ferrets and
mice recovering from infection are commonly immune to reinoculation of
the same strain of virus and
also to others of the same type. This effect is not permanent for, as
well demonstrated in the ferret, after a few
months, even though antibodies are present in the blood, reinoculation
may again cause febrile illness, with
destruction of the respiratory epithelium although pulmonary lesions do
not ordinarily develop. The general clinical
and epidemiologic experience of man with influenza has resulted in the
conclusion that immunity to the disease is of
a transient nature; the evidence has always been clouded, however, by
lack of knowledge of the agent involved.
Nevertheless, the experimental data in man and lower animals are in
accord. The fact that many of the human
patients have antibodies to virus of the same type before, or at the
time of, onset of influenza is clear evidence of
previous experience with the agent. This knowledge, together with the,
realization that there are two or more distinct
types of virus and many variations of strains within the types,
presents a formidable array of problems.

On the other
hand, mice can be readily immunized by intraperitoneal vaccination of
active or inactive virus and less
readily by subcutaneous inoculation; they become resistant even after
infection with virus not sufficiently well
adapted to cause severe disease. Ferrets, too, can be vaccinated but
usually less effectively than mice. In 1935,
Francis and Magill 54 demonstrated that, virus cultivated
in tissue
culture can be given to man subcutaneously or

intracutaneously without
eliciting signs of infection but resulting in the development of
antibodies which reach a
peak in about, 14 days and are maintained for months. The levels
attained, the curve of development, and the
persistence are quite parallel to those observed in subjects undergoing
the actual disease; hence, if immunity in man
is correlated with antibodies as it is in other animals, the results of
vaccination strongly suggest that resistance in
man could be similarly effected. In this background of information lay
a basis for efforts toward prophylactic
immunization. Before the advent of the Commission on Influenza,
different investigators had undertaken further
studies of vaccination with preparations of virus from tissue culture,
mouse lung, and chick embryo.55 In
each
instance, vaccination had resulted in antibody formation, but the
protective value against the disease had not been
clearly established; nevertheless, some of the results had suggested a
beneficial effect.

Organization for Researchin
War Period

The
onset of
war in Europe met in the United States a firm commitment of neutrality.
However, with the progressive
victories of the German armies, it became apparent that
American democracy must be prepared for its own defense. Preparation
meant more than the induction of men and the manufacture of materials.
It meant the creation of forces
trained in advance and maintained in a state of
effectiveness. No longer did events await the arrival and
the preparation of volunteers in the
numbers now required. Manpower was important.

It is commonly
said that the medical knowledge of one war has usually been forgotten
and bitterly relearned in the
next. The microbial enemy has often been more destructive than lead and
steel. Certainly it is true that personal
courage and indifference to risk have frequently been the substitute
for sanitary and other preventive measures. But
preparedness is medical too. In this instance, the history of
respiratory disease in World War I in a nastily mobilized
army without adequate provision for mass phenomena of disease had left
its memory. The improvised efforts to
meet a terrible situation had been splendid, but they emphasized the
need to view the possible problems in ad-

vance, to watch for signs of their development, and to seek control
methods for early and extended application. Moreover, much greater
scientific knowledge of specific approaches toward the prevention or
treatment of epidemic infection had developed. The interest of many
capable investigators was already moving in these directions. In
addition, many problems could, because of special circumstances, be
adequately studied only under military conditions. The Surgeon
General's Office was not only aware of these facts but acutely
interested in applying the concepts to the profit of the actively
growing military forces. Under these influences, the Board for the
Investigation and Control of Influenza and Other Epidemic Diseases in
the Army was initiated by the Preventive Medicine Division (fig.2),
and the Commission on Influenza was organized under the Board.
Much of the research and observations relating to influenza was
conducted by the Commission, but its functioning was at each step
dependent upon the financial aid from the Board and the strong and
imaginative support furnished by General Simmons, Brig. Gen. Stanhope
Bayne-Jones, and others of the staff, and the splendid cooperation of
the personnel of many organizations in which work was undertaken.

From the start, emphasis was placed on a broad program of study of
epidemics and of control measures as shown by the initial outline
presented by the Commission on Influenza to the Board on 27 and 28
February 1941:

I. Study of Control Measures.
I. Hygienic and Environmental Controls.
a. Influence of housing, size of
cantonments, troop movements.
b. Isolation of individual or
post; the use of masks.
c. Disinfection-sterilization of
dishes, sterilization of air with
aerosols or ultraviolet light.

2. Specific Control.
a. The efficacy of vaccination
against influenza virus infection in
man.
b. Prophylactic use of immune
serum.

II. Study of Epidemics.
1. Clinical.
a. Attempts to establish clinical
criteria for differentiation of
disease caused by different types of influenza virus or by other agents.
b. Possible study of
chemoprophylaxis of bacterial complications.

2.
Epidemiological.
a. To ascertain incidence of
immunes, subclinical and clinical cases in
correlation with laboratory studies.
b. The method of introduction,
the factors influencing spread, and the
pattern of epidemics.

4. Virus.
a. To identify virus in
epidemics, especially in recurrent waves, and
the relation of illness to the immunologic state.
b. To evaluate importance of
factors other than circulating antibody in
resistance.
c. To institute prophylactic
measures.
d. To ascertain complications
caused by virus alone. .

5. Pathological
a. To correlate the picture in
fatal cases with etiological studies.
b. To search for diagnostic
criteria when illness was not caused by
known virus.

6. Cooperative studies with other
Commissions, especially in the
field of complications and chemotherapeutics.

In order to meet these objectives, a more detailed
pattern of organization and plan of operation was designed by which the
United States was divided geographically into eastern, midwestern, and
far western areas, and the members of the Commission were largely
divided in the same manner. It was proposed that, in the event of a
severe epidemic, an equipped, highly qualified team of investigators
comprising a clinician, a pathologist, an epidemiologist, a
bacteriologist, and a virologist would enter the field in each area and
function as an investigative unit to gain a rounded picture of the
epidemic disease and special knowledge of the different aspects of the
problem.

Interim studies would deal largely with practical
approaches to the improvement of control procedures. At the
meeting of the Board, 19 to 21 June

117

1941, specific authorization was given for the following interim
investigations: (1) Experimental trial of influenza vaccine should a
promising vaccine be available and suitable opportunity arise; (2)
studies of the efficacy of respiratory masks; and (3) laboratory
studies of materials and samples collected in the field bearing on the
etiology, epidemiology, and immunology of influenza and its
complications. The problems of air sterilization were referred to a
newly formed Commission on Cross-infections in Hospitals. An
appropriation of $25,000 for interim and $30,600 for field studies was
voted. The original estimate was sharply reduced by the offer of the
Rockefeller Foundation to provide, without cost, the facilities and
participation of their laboratories in New York and San Francisco.
Mobile laboratories were considered unnecessary because of the
availability of corps area laboratories.

Here was provided a coordinated alert in which all
members of the Commission would report immediately any outbreaks of
respiratory diseases so that investigations could be rapidly instituted
and in which civilian personnel with special interests were prepared to
study influenza from a variety of approaches in their own laboratories
or, in the field, to assist the Army during epidemics as ordered by The
Surgeon General. A statement summarizing the current status of
influenza and its control was prepared and published in Circular Letter
No. 124, Office of the Surgeon General, on 23 December 1941.

Studies of Vaccination

Although a great deal of the subsequent discussion
is concerned with the problem of vaccination against influenza, many of
the major problems presented in the original plan were integrated into
this broad concept in which research in the problems of the disease and
the virus constitute the basis for studies in vaccination.

Intranasal
vaccination.-Two major concepts of vaccination were considered.
The one was intranasal introduction of active virus so attenuated as to
give mild or subclinical infection with the expectancy that
satisfactory resistance would develop. This would simulate
natural conditions and should contribute any advantage, including
possible alterations in tissue susceptibility, which accompanied actual
infection. Preliminary observations had indicated that virus
which had been maintained for long periods in tissue culture could be
used without eliciting symptoms but the serologic response was quite
irregular. The pathogenic balance was, therefore, of importance.
Moreover, the objection was raised that within military forces active
virus might be enhanced by passage and give rise to outbreaks of the
disease. Nevertheless, in an approach to the problem, 3 series of
10 human subjects each were sprayed with different doses of type B
virus from allantoic fluid. 56 After
incubation periods of 18 to 24 hours, 27 of 30 men developed clinical
influenza and with recovery showed significant rises in circulating
antibody. But when retested

4 months later with the same virus, one-third again developed acute
illness comparable to the first, while others had milder illness.
Inactivated virus caused no reaction. There was thus no uniform, firm
immunity acquired under the condition of the study.

Subcutaneous
vaccination.-The second approach to which greatest attention was
given was that of subcutaneous vaccination. The various studies
previously carried out (p.113) had shown that virus administered in
this manner could stimulate good levels of antibody, and some
indications of resistance had been observed in man under epidemic
conditions. Although active virus could be given, the problems of
stability of virus, bacterial sterility and possible viral
contaminants, and storage and distribution were practical objections.
Finally, attention was centered upon the preparation of vaccine
containing type A and type B viruses from the allantoic fluid of
infected chick embryos. High titers of virus were available, and
the problem here became one of developing procedures and
production. For the latter purpose, the interest of commercial
biologic firms was enlisted. The development of the program is given in
detail in the history of the Commission oil Influenza, and this
discussion will present only summaries of the actual trials. The
principles at all times were to provide for a supply of practicable
vaccine; the selection of a homogeneous, stable vaccine; uniform
procedure; close observation by highly competent investigators;
confirmation of diagnosis by etiologic and serologic methods; and
adequate controls at all steps.

Studies in 1941-42

Authorization was given for a study, under the
immediate supervision of Dr. Eaton, in troops in California if the
opportunity for a satisfactorily controlled experiment arose. Two
thousand doses of a vaccine prepared from chick embryos were made
available by Drs. J. H. Bauer and G. K. Hirst of the laboratories of
the International Health Division of the Rockefeller Foundation. This
effort was abandoned in January 1942 because of change in conditions
due to our entry into war.

Studies in 1942-43

In addition to evidence that inactivation of virus
caused a reduction in antigenic potency, data of Hirst, Rickard,
Whitman, and Horsfall 57
indicated that within limits higher antibody levels were reached in man
with preparations of virus concentrated from allantoic fluid by
centrifugation. Hirst, Rickard, and Whitman, 58 and Hare,
McClelland,
and Morgan 59 described the concentration of virus by
collection on a
precipitate which formed when previously frozen material was allowed to
thaw.

The probabilities of an epidemic in this period were
high since it would be in keeping with the 2-year cycle of identified
influenza A since 1932-33. A field trial of vaccine prepared by this
method was then planned for the winter of 1942-43.

Cornell study.-Drs.
Magill, N. Plummer, and W. G. Smillie and their associates undertook a
study in the student body and faculty at Cornell University, Ithaca, N.
Y. Recruitment into the study was on a voluntary basis with
administration of vaccine or control material of normal allantoic fluid
subcutaneously. Of a total of 2,885 persons, 1,672 received vaccine and
1,213 control material. Great difficulty was encountered by the firm
which undertook the preparation of precipitated vaccine, and Dr. Hirst
aided by providing 1,000 doses from the Rockefeller Foundation. Another
lot of unconcentrated type A vaccine was also used. Careful
clinical, viral, and serologic observation was maintained on
respiratory illness in the population. No virus was isolated. No
influenza was detected although serologic evidence suggested that a few
infections with influenza B occurred. No difference in incidence, of
any class of respiratory disease was noted among the vaccinated and
control groups. Good antibody responses to vaccination were maintained
during the 4 to 5 months' observation. Reactions with systemic symptoms
of fever, aches, and other conditions were observed in approximately 10
percent of those receiving either concentrated or unconcentrated
vaccine and in 2 percent of the controls.

Michigan study.-In
two institutions, a study was arranged to test the, cold-precipitated
type of vaccine. Owing to the difficulty mentioned in manufacture,
attention was turned to vaccine prepared by concentration of virus from
allantoic fluid by adsorption to, and elution from, erythrocytes of the
infected embryo.60 In this
manner, an eightfold to tenfold concentration of virus could be
obtained in salt solution while leaving a large proportion of
extraneous material behind. The virus was readily inactivated by
0.05 percent formalin, and sterility was relatively easy to
control. Its potency was equal to that prepared by freezing and
thawing. The greater ease of its production resulted in obtaining
sufficiently large amounts of finished vaccine from the same commercial
firm. Each 1.0 cc. contained the virus obtained from 5.0 cc. of type A
fluid and from 5.0 cc. of type B fluid.

In late December and early January, 3,914 persons
received 1.0 cc. vaccine and 3,909 alternately received control
solution. The expected epidemic of influenza A did not occur, although
in one institution influenza B at a subclinical level was detected
(p.95). Antibodies to both viruses rose after vaccination and
diminished
slowly over a year's time but still remained above prevaccination
levels. Data oil antibody levels of the same persons before, and at
intervals after, vaccination with combined A and B vaccine are
presented in table 21.

The results of the year's endeavors had given
information that concentrated vaccine was producible by two different
methods of preparation and, in addition, that after eluate vaccine a
high level of antibody was maintained for an extended period-a year at
least. This observation was amply confirmed in later studies.

To gain information of the protective effect of
vaccine by direct means, a test of immunity to induced influenza A and
influenza B was undertaken by spraying with active virus groups of the
vaccinated and control populations.61 The results
demonstrated a high degree of protection against influenza B. There was
an incidence of 10 percent in those vaccinated as long as 4 months
earlier and in 40 percent of the controls, a greater resistance than
had been obtained by actual experimental infection with the same
virus. In the case of influenza A, vaccination 2 weeks before
test reduced the incidence from 50 percent in the controls to 16
percent in the vaccinated, although vaccination 4 months earlier had a
less definite effect. There was, therefore, definite information of
immunizing influence of the vaccine produced by elution. Stokes and
Henle 62 had also demonstrated in a similar fashion
the protection of a group of children from experimentally induced
influenza A after subcutaneous vaccination with vaccine prepared from
allantoic fluid.

Other studies.-Dr.
Hirst undertook a study involving 8,058 persons in institutions who
received vaccine concentrated by freezing and thawing with a similar
number of designated uninoculated controls. The absence of
epidemic influenza thwarted an evaluation of effect.63 Another
study by Dr. Eaton with alum-precipitated vaccine met the same
situation, but he showed that the antibody titers were comparable to
those obtained with the other preparations.

The desirability of field studies of vaccination in
military units was increasingly evident and for this reason
authorization was obtained to conduct investigations in Army
Specialized Training Program units. They were stable populations
and subject to constant, uniform observations. It was possible to
obtain participation of entire units so that vaccinated persons and
controls could be properly designated rather than depending upon the
less desirable and unpredictable basis of volunteers. Different
members of the Commission were responsible for the work with units in
different parts of the country; however, the same vaccine, the same
record system, the same plan of observation, including clinical
criteria, and viral and serologic studies were agreed upon. Alternate
men in each unit were to receive vaccine and control material
subcutaneously. The vaccine prepared by the elution
method contained 50 percent type B (Lee) virus and 50 percent type A
virus. Of the latter, half was the PR8 strain and half the Weiss
strain, which had been isolated from a sporadic case in Mav 1943, and
was employed because of the possibility that it might represent a
forerunner of a subsequent strain.64

Six studies in nine ASTP groups constituting
approximately 12,500 men were established with vaccination scheduled
for October or November. Again, emphasis was placed upon a continuous,
intensive watch for the occurrence of influenza. A coordinated system
was arranged for sampling of respiratory illness in the selected units
and throughout the different service commands with regular reporting of
results. The epidemic of influenza A was promptly detected in the Sixth
and Seventh Service Commands between 15 and 20 November at which time
vaccination of the study groups was, with one exception, either
completed or in progress. It spread rapidly through the service
commands with sharp peaks during the early weeks of December, but in
the Fourth, Eighth, and Ninth Service Commands the epidemic was more
prolonged and at lower levels than in the others. It was
essentially over by T January. The results of the study gave conclusive
evidence, because of the carefully controlled procedures, that
vaccination had exerted a sharply protective effect against epidemic
influenza A (table 22).65

The final figures differ little from those of the
preliminary summary. The total incidence based upon admissions was 7.3
percent among 6,198 controls and 2.2 percent among 6,253 vaccinated, a
ratio of 3.3:1. No fatalities occurred in the study groups and
there were few cases of pneumonia.

Other data of importance were also obtained.
It was found that the epidemic was essentially a pure one in that 80 to
90 percent of cases were identifiable as influenza A. In addition
to the incidence of 8 to 10 percent as measured by the admissions, it
was shown that as high as 35 to 40 percent of the control population
had undergone infection, much of it subclinical. This

TABLE 22.-Summary of
clinical evaluation of vaccination against
influenza, 1943 (combined totals of all results)
is of importance in estimating the immunizing effect of either vaccine
or of the natural infection. There was a definite trend indicating the
tendency for the highest frequency of disease to occur in that portion
of the vaccinated population with the lowest antibody titers; the same
relation existed in the unvaccinated population. There were suggestions
that this correlation was more distinct when antibodies were measured
against strains from the epidemic rather than against the PR8 strain of
the vaccine.

The vaccine induced localized erythema, edema, and
heat in the majority of those inoculated; some systemic manifestations
such as mild aching and chilliness occurred in as many as 25 to 30
percent, and 1 to 2 percent of some groups were sick enough to report
to sick call. In the total vaccinated population, four instances
of apparently allergic reactions were recorded.In two instances, the
epidemic began while vaccination was being done; it was observed that
the incidence curves began to separate in the vaccinated and controls 5
to 8 days after vaccination, indicating that after this interval the
vaccine effect had begun. In two groups, streptococcal infection was
prevalent, but no accentuation in severity of disease took place. The
duration of protective effect was not demonstrable by these studies,
but it was uniformly noted that, over several months only a mild fall
in the postvaccination antibody titers to type A or type B virus took
place. Two other groups which had been vaccinated the previous year
were observed during this epidemic with results indicating that vaccine
had exerted a protective influence even after that

123

interval. 66 The suggestion was made
that the California study had been less decisive than the others
because of a longer interval between vaccination and the epidemic
occurrence, but this does not appear to be valid.

The success of the study in evaluating the vaccine
and in gaining a large amount of accessory information was the result
of a carefully planned program by highly interested and qualified
investigators who maintained a uniformity of procedure and observation
while using adequate controls in each please of the study. The speed
with which the epidemic developed, spread, and declined strongly
demonstrates the difficulty to be encountered if the study is not
established in advance of the epidemic; otherwise, it is probable that
the opportunity will have passed before the work can be done.

With the termination of the 1943 epidemic, influenza
apparently disappeared in the United States and, although the
continuous alert for detection was maintained and expanded, no field
studies were planned for 1944. The question of providing suitable
vaccine for use throughout the Army was being studied. The problem of
reactions was investigated, with a clear demonstration that this
typhoidlike effect was strictly related to the amount of virus in the
vaccine and that the amount contained in the eluate vaccines used in
1943 was about the limit tolerable.67 The increase in antibody titer was not directly proportionate to the
amount of virus; 2.0 mg. of virus protein resulted only in a twofold
increase in titer over that obtained with 0.2 mg. It was clear,
nevertheless, that too small a dose did not elicit adequate response,
and it was concluded that a range between 0.2 and 0.5 mg. of "estimated
virus protein" was the most practicable from all
considerations-alltibody response, percentage of reactions, and cost of
production. The previous vaccines appeared to fall in this
range. Concentration of vaccine by centrifugation was studied,
standards for its production were devised, and it was accepted as an
alternative procedure for Army vaccine.

Studies in 1945

In view of the increasing prevalence of influenza B
noted in 1945, the recommendation was made through the Epidemiological
Board that vaccination be carried out in the Army in October unless
events warranted its earlier use. Final approval of The Surgeon
General and of the Secretary of War was given in August. In some areas
of the Pacific, vaccination had already been instituted because of
higher incidence of the disease, but the program was carried out almost
uniformly in all Army personnel in all theaters of operations during
October and November 1945 with vaccine prepared by the elution method.

Because of the uniform regulation concerning
vaccination throughout the Army, no controlled study could be
established within that service. However, in two locations
circumstances were such that an opportunity for evaluation arose.
Naval personnel were not vaccinated, otherwise V-12 units were closely
comparable to ASTP units, and the university agency for supervision of
their health was usually the same. At the University of Michigan
and at Yale University, the naval units and the ASTP units were under
observation at the time the sharp epidemic of influenza B developed in
November and December 1945. The opportunity was thereby provided for a
comparison of the occurrence of influenza in the two organizations. 68 The results based upon admissions to the infirmaries were
striking. As clearly demonstrated in table 23, vaccination had
been highly protective against epidemic influenza B. The effect was
even sharper than the results with the same vaccine against influenza A
in 1943. Etiologic studies demonstrated that the epidemic was limited
to type B virus. The strains of type B virus showed serologic
characteristics which readily separated them from the vaccine strain
(Lee) although the latter gave adequate cross-immunity. Two further
indications were obtained. The first is in accord with earlier data
that type B is a better immunizing agent than type A strains. The
second is that vaccination of a total group gives better protection to
the group than when, as in 1943, only half the group is vaccinated.
Comparison of a completely vaccinated group with a completely
unvaccinated unit might also yield a sharper differential possibility
also suggested in 1943 when the incidence in certain unvaccinated
companies was found to be strikingly higher than in the unvaccinated
half of the study groups. Thus, vaccination of half a closely
associated unit would have a limiting effect upon the risk to the
unvaccinated portion so as to

reduce the incidence ill the latter below that of a totally untreated
population. There is no indication in the tabulated data that
resistance of the vaccinated unit was any different in the late stages
of the epidemic than earlier. Moreover, the close, similarity of the
results in the two institutions adds to their significance.

Further effort to gain information on the effect of
vaccine upon the incidence of disease in the Army was presented in ASF
monthly progress reports. Analysis was made of respiratory disease
rates in Army and Navy personnel in the United States during the 1945
epidemic, when vaccine had been widely administered in the Army but the
Navy remained unvaccinated, and compared them with the experience of
the two services in 1943 when neither lead been vaccinated. Whereas, in
1943, the incidence of admissions for common respiratory disease and
influenza in the Army was 117 percent of that of the Navy at the peak
of the epidemic, in 1945 the Navy rate at the peak was 173 percent of
that of the Army, or, conversely, the Army rate was only 57 percent of
the Navy's. While the Army rate in 1945 was only 27 percent of that
observed in 1943, the Navy rate was still 55 percent (chart 15).

The excess rate over the preepidemic level for
common respiratory diseases in the Army in 1945 was only about 16
percent of that in 1943, while in the Navy it was still about 46
percent of the 1943 excess. The comparison with previous
experience between the two services points out: "The increase in Army
morbidity should have been just twice what was actually reported for
November and December. A large part of the 50 percent increase
not prevented may have consisted of common colds rather than
influenza." The latter suggestion is further supported by the fact that
the increased incidence in the Army did not abruptly subside as it did
in the Navy, indicating that it might be largely the seasonal rise of
common respiratory disease. It was not markedly different from that of
1944 when little influenza was observed. Moreover, the contrast, held
when the incidence in naval districts and Army service commands was
compared geographically. In the areas of the Fifth, Sixth, and Seventh
Service Commands and the Ninth Naval District, where the ASTP study was
convincing, the epidemic peak in the Navy was two and one-half times as
high as in the Army (chart 16). The analysis indicates that
vaccination was not complete in the Army and that most cases of
confirmed influenza were in unvaccinated men. Further analysis
emphasizes that the incidence curve in the Army did not differ
strikingly from that of 1944, while the Navy experienced sharp
epidemics. "In summary it may be said that all available evidence
points to a considerable saving in morbidity. It seems entirely fair to
judge the efficacy of the vaccination program on the basis of the
period when the epidemic was in progress. One can only
conclude that the epidemic of mild influenza B touches the Army only
very lightly because of the protection afforded by the vaccine." 69

The field studies of vaccination against influenza
led to an application of the procedure in the entire Army. Their
development was guided by evidence as it could be acquired and upon the
pattern of the scientific experiment with proper control. Even
when an ideal study could not be planned in advance, active
investigators, continuously on the alert, could seize the unplanned
opportunity to gain evidence.

Other pleases of research important to the problem
of influenza were being carried on. A serious question was whether
drugs effective in the treatment of bacterial pneumonia would be
efficient when those pneumonias were as sociated with infection with
influenza virus. Laboratory investigation lead shown that the virus was
not affected by sulfonamides or penicillin, but studies by Drs. Barry
Wood and Carl Harford 70 demonstrated that
sulfonamides would control pneumococcal infection in rats and mice in
which pneumonia was produced by combined virus and bacteria. The
clinical experience first

recorded by Eaton and Meiklejohn 71 during
the 1943 epidemic developed also to establish the fact that the
bacterial pneumonias encountered in influenza patients could be
effectively treated with sulfonamides. The subsequent availability of
penicillin enhanced the treatment, and a major threat was thus subject
to control.

There still persisted a great possibility that H. Influenzae might be seriously
involved. For this reason, continuous studies were conducted on this
organism, its prevalence, and its characteristics, by Dr. Hattie
Alexander, and a diagnostic center was maintained. 72
No significant participation of that bacterium was encountered.

The idea that prophylaxis of influenza by use of
intranasal spray with immune serum had developed. The concept was that
antibody provided at the site of virus introduction might protect the
susceptible epithelium of the respiratory tract. A series of studies in
mice showed that it was possible; it was not effective in
ferrets. Smorodintseff and his associates 73 had reported that influenza in mice could be prevented in this
manner. In 1943, through the Commission on Influenza, a
significant series of studies was conducted to determine whether human
sera with high titers of antibody given by intranasal spray could
prevent experimental infections with influenza virus. The studies
were conclusive and indicated no prophylactic effect. The details are
given in the history of the Commission on Influenza. The idea is,
however, still of interest for further study.

The investigations of atypical pneumonia originally
instituted through the Commission on Influenza gave rise to the
Commission on Acute Respiratory Disease, and those on air sterilization
were developed by the Commission on Air-Borne Infection. Details
of other studies are also included in the histories of the respective
Commissions.